Anti-cancer drugs in a form presently available on the market all have a problem of relating to a low drug-release rate. Although a low drug-release rate can decrease the side effects of anti-cancer drugs, the therapeutic effect of the drug cannot be increased.
Neovascularization of tumor tissue and inflammatory tissue is incomplete, and thus cell metabolic products cannot be easily excreted to a patient's circulatory system. Therefore, pH values of such tissues are lower than those of normal tissues, and are about 6.8-7.2. In addition, pH values of environments of endosomes and lysosomes in a cell are about 4.0-6.5, and if nano-carriers can be rapidly controlled to release a drug, the problem of low drug release rates among nano-carrier drugs can be solved. Furthermore, for some biotechnological drugs, such as peptides, proteins, and gene fragments, if this kind of drug is released from endosomes to cytoplasma, and is not transported to lysosomes, the activities of such drugs can be increased.
Hyaluronic acid is a polymer of disaccharides, themselves composed of D-glucuronic acid and D-N-acetylglucosamine. In the hyaluronic acid, D-glucuronic acid and D-N-acetylglucosamine are linked via β-1,3 glycosidic bonds, while disaccharides are linked via β-1,4 glycosidic bonds. Generally, molecular weights of hyaluronic acid range from 5,000 to 20,000,000 Da. Commercialized hyaluronic acid is usually in the form of sodium salt thereof, i.e. sodium hyaluronate.
Natural hyaluronic acid is a water-soluble polymer, has excellent variable properties for being a drug carrier, such as bio-compatibility, non-immunogenicity, natural degradation by an enzyme in the body, having a lot of functional groups of —OH, —COOH and —CH, OH, etc., and capable of performing covalent modification. Therefore, according to the afore mentioned information, it is known that hyaluronic acid is able to be an excellent drug carrier.
At present, a novel drug delivery system that has high bio-compatibility, and that can be designed to release a drug only in an appropriate environment, is needed.